The ultimate objective of the proposed investigation is to elucidate the mechanism by which the "non-cytopathogenic" lactic dehydrogenase-elevating virus (LDV) replicates in mammalian cells, how virus replication operates within the framework of the regulatory processes of the host cells without causing overt disease and how this virus may synergistically, with other viruses or agents, affect the host immune system or alter the development of tumors. The question of how LDV affects the cellular and humoral immune systems and blood enzyme clearance of the host, and enchances tumor induction by RNA tumor viruses will be investigated by studying the replication of LDV and Friend murine leukemia virus (F-MLV) in mice, in B ad T lymphocytes and in cultures of mouse macrophages and of spleen and lung cells. Antibodies prepared to LDV in other experimental animals and also isolated from chronically infected mice will be used to develop a method for the titration of LDV and to detect LDV replication in individual cells in culture or in tissues removed from infected animals. The mechanism of synthesis of LDV RNA will be studied in actinomycin-treated cell cultures. Studies on the physical-chemical characteristics of LDV will be continued. Amino acid and glucosamine-labeled virus will be purified and the nature of the viral proteins and their location within the virion will be determined. It will also be investigated whether defective particles play a role in the chronic infection of mice and cultures with LDV. A search will be made in other species, including man, for viruses of a type similar to LDV. Human blood samples will be screened for elevated enzyme levels and suspicious samples will be analyzed for virus by inoculation into human cell cultures. BIBLIOGRAPHIC REFERENCES: Brinton-Darnell, Margo and Plagemann, P.G.W.P. Structure and chemical-physical characteristics of lactate dehydrogenase-elevating virus and its RNA. J. Virol. 16:420, 1975. Tong, S.L. and Plagemann, P.G.W.P. An autoradiographic method for detection of lactic dehydrogenase-elevating virus (LDV)-infected peritoneal macrophages. Abstr. Ann. Meeting ASM, S-36, p. 210, 1976.